Impact of Cystic Fibrosis Transmembrane Conductance Regulator on Malignant
Properties of KRAS Mutant Lung Adenocarcinoma A549 Cells.
10.3779/j.issn.1009-3419.2018.02.03
- Author:
Hui LI
1
;
Ying WANG
1
;
Jiali YANG
2
;
Xiaoming LIU
2
;
Juan SHI
2
Author Information
1. College of Clinical Medicine, Ningxia Medical University, Yinchuan 750004, China.
2. General Hospital of Ningxia Medical University, Yinchuan 750004, China.
- Publication Type:Journal Article
- Keywords:
A549 cells;
Cystic fibrosis transmembrane conductance regulators;
Lung neoplasms
- MeSH:
A549 Cells;
Adenocarcinoma;
pathology;
Adenocarcinoma of Lung;
Cell Movement;
genetics;
Cell Proliferation;
genetics;
Cystic Fibrosis Transmembrane Conductance Regulator;
metabolism;
Humans;
Lung Neoplasms;
pathology;
Mutation;
Neoplasm Invasiveness;
Neoplastic Stem Cells;
pathology;
Proto-Oncogene Proteins p21(ras);
genetics
- From:
Chinese Journal of Lung Cancer
2018;21(2):89-98
- CountryChina
- Language:Chinese
-
Abstract:
BACKGROUND:The incidence of lung cancer is gradually increased, and the cystic fibrosis transmembrane conductance regulator (CFTR) has recently demonstrated to have an implication in the deoncogenesis and malignant transformation of many types of cancers. The aim of this study is to investigate impacts of CFTR on the malignant features of lung adenocarcinoma A549 cells.
METHODS:The capacity of cell proliferation, migration, invasion and clonogenicity of non-small cell lung cancer A549 cells were detected by CCK8 cell proliferation assay, cell scratch assay, Transwell cell invasion assay and clone formation assay, respectively. Meanwhile, the effect of CFTR gene on the expression of cancer stem cell related transcriptional factors was also detected by immunoblotting (Western blot) assay.
RESULTS:An overexpression of CFTR gene in A549 cells significantly inhibited the malignant capacity of A549 cells, including potencies of cell proliferation, migration, invasion and colony formation; while knockdown of CFTR gene expression by RNA interference in A549 cells resulted in an opposite effect seen in above cells overexpressing CFTR gene. Mechanistically, immunoblotting assay further revealed that the ectopic expression of CFTR gene led an inhibitory expression of stem cell-related transcriptional factors SOX2 and OCT3/4, and cancer stem cell surface marker CD133 in A549 cells, while a knockdown of CFTR expression yielded a moderately increased expression of these gene. However, an alteration of CFTR gene expression had neither effect on the expression of putative lung cancer stem cell marker aldehyde dehydrogenase1 (ALDH1), nor the frequency of ALDH1A-positive cells in A549 cells, as ascertained by the immunoblotting assay and cytometry analysis, respectively.
CONCLUSIONS:The CFTR exhibited an inhibitory role in the malignancy of lung adenocarcinoma A549 cells, suggesting that it may be a novel potential target for lung cancer treatment. However, its functions in other lung adenocarcinoma cell lines and its underlying molecular mechanisms require further investigation.
